Identification of potential inhibitors of thymidylate synthase (TS) (PDB ID: 6QXH) and nuclear factor kappa-B (NF–κB) (PDB ID: 1A3Q) from Capsicum annuum (bell pepper) towards the development of new therapeutic drugs against colorectal cancer (CRC)

Q2 Physics and Astronomy

Physical Sciences Reviews Pub Date : 2023-03-21 DOI:10.1515/psr-2022-0281

M. Olajide, M. Abdul-Hammed, I. Bello, I. O. Adedotun, Tolulope Irapada Afolabi

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引用次数: 0

Abstract

Abstract Colorectal cancer is the third most deadly cancer globally. Drug resistance and attendant side effects make the available standard anti-colorectal cancer drugs against target receptors inefficient. Phytochemicals from medicinal plants are safer, cheaper, effective, and heal diseases from the cellular level. This study is aimed at identifying potential inhibitors of thymidylate synthase (TS) and nuclear factor kappa-B (NF–κB) target receptors from Capsicum annuum towards the development of new therapeutic drugs against colorectal cancer via in silico approach. One hundred and fifty (150) ligands previously reported from Capsicum annuum were downloaded from the PubChem database and were subjected to chemo-informatics analyses such as ADMET, drug-likeness, oral bioavailability, bioactivity, and PASS prediction to ascertain their therapeutic and safety profile before docking. The ligands that passed the analyses were docked against TS and NF–κB in duplicate using a creditable docking tool (PyRx). Raltitrexed and emetine were used as the standard drug inhibitors for TS and NF–κB, respectively. The results obtained from this study showed that feruloyl-beta-D-glucose (8.45 kcal/mol), 5-O-caffeoylquinic acid (−8.40 kcal/mol), 5-O-caffeoylquinic acid methyl ester (−7.89 kcal/mol), feruloyl hexoside (−7.40 kcal/mol), O-glucopyranoside (−7.55 kcal/mol), and quercetin (−7.00 kcal/mol) shared the same binding pocket with TS while feruloyl-beta-D-glucose (−7.00 kcal/mol), chlorogenic acid (−6.90 kcal/mol), 5-O-caffeoylquinic acid (−6.90 kcal/mol) and feruloyl hexoside (−6.50 kcal/mol) shared the same pocket with NF–κB. These compounds were selected as best hits due to their excellent inhibitory efficiency and chemoinformatic profiles. Thus, the compounds may function as prospective lead compounds for developing a new anti-colorectal cancer drug.

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辣椒胸苷酸合成酶(TS) (PDB ID: 6QXH)和核因子κ b (NF -κB) (PDB ID: 1A3Q)潜在抑制剂的鉴定及其对结直肠癌治疗新药开发的影响

结直肠癌是全球第三大致命癌症。耐药和随之而来的副作用使得针对靶受体的标准抗结直肠癌药物效率低下。药用植物中的植物化学物质更安全、更便宜、更有效，能从细胞层面治愈疾病。本研究旨在通过芯片技术从辣椒中寻找胸腺苷酸合成酶(TS)和核因子κ b (NF -κB)靶受体的潜在抑制剂，以开发新的结直肠癌治疗药物。从PubChem数据库中下载了150个先前报道的辣椒配体，并进行了化学信息学分析，如ADMET、药物相似性、口服生物利用度、生物活性和PASS预测，以确定对接前它们的治疗性和安全性。通过分析的配体使用可靠的对接工具(PyRx)分别与TS和NF -κB对接。以雷替曲塞和艾美汀分别作为TS和NF -κB的标准药物抑制剂。结果表明:阿魏酰- β - d -葡萄糖(8.45 kcal/mol)、5- o -咖啡酰奎宁酸(- 8.40 kcal/mol)、5- o -咖啡酰奎宁酸甲酯(- 7.89 kcal/mol)、阿魏酰己糖(- 7.40 kcal/mol)、o -葡萄糖苷(- 7.55 kcal/mol)和槲皮素(- 7.00 kcal/mol)与TS具有相同的结合袋;阿魏酰- β - d -葡萄糖(- 7.00 kcal/mol)、绿原酸(- 6.90 kcal/mol)、阿魏酰- β - d -葡萄糖(- 7.00 kcal/mol)、阿魏酰- β - d -葡萄糖(- 7.00 kcal/mol)、阿魏酰- β - d -葡萄糖(- 7.00 kcal/mol)、阿魏酰- β - d -葡萄糖(- 7.00 kcal/mol)、阿魏酰- β - d -葡萄糖(- 7.00 kcal/mol)、5- o -咖啡酰奎宁酸(- 6.90 kcal/mol)和阿魏酰己糖(- 6.50 kcal/mol)与NF -κB共用一个口袋。这些化合物因其优异的抑制效率和化学信息学特征而被选为最佳hit。因此，该化合物可作为开发新型抗结直肠癌药物的前瞻性先导化合物。

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来源期刊

Physical Sciences Reviews MULTIDISCIPLINARY SCIENCES-

CiteScore

2.40

自引率

0.00%

发文量

173